ArticleCancer research and treatment2023
ARID1A Mutation from Targeted Next-Generation Sequencing Predicts Primary Resistance to Gemcitabine and Cisplatin Chemotherapy in Advanced Biliary Tract Cancer.
Article in Cancer research and treatment, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 14 citations in OpenAlex.
- Artificial Intelligence-Powered Human Epidermal Growth Factor Receptor 2 Quantification and Clinical Outcomes in Human Epidermal Growth Factor Receptor 2-Positive Biliary Tract Cancer Treated With Trastuzumab Plus Folinic Acid, Fluorouracil, and Oxaliplatin.JCO precision oncology · 2025Trial
- Evolving precision: Updates in targeted therapy for cholangiocarcinoma.Hepatology (Baltimore, Md.) · 2026Review
- Trastuzumab plus nivolumab with gemcitabine and cisplatin as first-line therapy for HER2-positive unresectable biliary tract cancer: a phase 1b/2 trial.Nature medicine · 2026Article
- Ex vivo drug screening and clustering of bladder cancers for pre-clinical treatment prediction.Communications medicine · 2026Article
- Biology-driven stratification of advanced biliary tract cancer treated with nab-paclitaxel plus gemcitabine-cisplatin: A prospective observational cohort study.Hepatology (Baltimore, Md.) · 2025Article
- Predicting cisplatin response in cholangiocarcinoma patients using chromosome pattern and related gene expression.Scientific reports · 2025Article
- Prognostic Role ofJCO precision oncology · 2025Article
- Chromatin-focused genetic and chemical screens identify BRPF1 as a targetable vulnerability in Taxol-resistant triple-negative breast cancer.Experimental & molecular medicine · 2025Article
- Establishment and genomic profiling of cholangiocarcinoma cells with functional characterization.Scientific reports · 2025Article
- Epidemiology and genomic features of biliary tract cancer and its unique features in Korea.Journal of liver cancer · 2025Article
- A mutational signature and ARID1A mutation associated with outcome in hepatocellular carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Genomic analysis of bladder urothelial carcinoma with osteoclast‑like giant cells: A case report.Molecular and clinical oncology · 2024Article
- ARID1A in Gynecologic Precancers and Cancers.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Advances in the study of the role of high-frequency mutant subunits of the SWI/SNF complex in tumors.Frontiers in oncology · 2024Review
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
purposeThere are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC. MATERIALS AND
methodsGenomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients' clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines.
results193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells.
conclusionIntegrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.
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